Neural Modulation Strategies in Neuroscience

Chemogenetics is a powerful and versatile neuromodulation strategy that enables remote, reversible control of defined cell populations through the use of engineered receptors and pharmacologically inert small-molecule ligands. This review synthesizes the current state of chemogenetic technologies, focusing on Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) and emerging ion-channel-based actuators, and outlines their molecular mechanisms, ligand pharmacology, and recent technical innovations. We examine the broad applications of these tools in disease modeling, behavioral neuroscience, and experimental therapeutics, as well as in biomedical contexts beyond the central nervous system. Particular attention is given to the role of chemogenetics in mapping and causally dissecting neural circuits, where it provides precise and reversible modulation of neuronal activity to elucidate the cellular substrates of behavior.

Comparisons with other neuromodulation techniques—such as optogenetics and electrical stimulation—are discussed, together with practical considerations including ligand selection, delivery strategies, and long-term applications. Finally, we highlight the translational trajectory of chemogenetic technologies, emphasizing ongoing advances that are bringing gene therapy-based neuromodulation closer to clinical application in neurology and psychiatry.